Hyperpolarized 13C-Pyruvate With or Without Hyperpolarized 13C, 15N-Urea Magnetic Resonance Imaging Scan for the Imaging of Prostate Cancer

PRIMARY OBJECTIVES:

I. To optimize the imaging sequences that maximize signal-to-noise ratio (SNR) and intra-tumoral conversion of HP 13C pyruvate to lactate (kPL) and HP 13C pyruvate to glutamate (kPG) in regions of tumor versus (vs.) adjacent benign tissue as assessed by multi-parametric MRI (mpMRI) imaging characteristics. (Part 1)

II. To perform HP 13C-MRI and measure the changes in tumoral kPL and kPG between baseline and 3-months and 1 year post-external beam radiation therapy (EBRT). (Part 2A)

III. To perform HP 13C-MRI and study the metabolic effects (changes in tumor kPL and kPG) between baseline and 4-12 weeks after initiation of systemic hormone therapy; and then 3-months and 1-year post-EBRT. (Part 2B)

IV. To perform HP 13C-MRI at time of biochemical failure and measure tumoral kPL and kPG, in previously EBRT treated patients, followed by MRI ultrasound (MR-US) fusion biopsy. (Part 3)

SECONDARY OBJECTIVES:

I. To evaluate the intra-patient variability in intra-tumoral kPL and kPG with repeated dose studies. (Parts 1-3)

II. To determine the association between peak intra-tumoral kPL observed on baseline imaging with serum prostate specific antigen (PSA). (Parts 2-3)

III. To determine the association between changes in intra-tumor kPL after 4-12 weeks of systemic hormone therapy and PSA response. (Part 2B)

IV. To compare and contrast intra-tumoral kPL and kPG with Prostate Imaging Reporting and Data System (PI-RADS) version 2 and individual mpMRI parameters including apparent diffusion coefficient (ADC) on diffusion-weighted imaging. (Parts 1-3)

V. To describe the frequency of upgrading of tumor with MR/US-guided fusion biopsy obtained following baseline HP-MRI exam. (Part 3)

VI. To further characterize the safety profile of HP C-13 pyruvate injections. (Parts 1-3)

VII. For patients imaged with HP 13C-MRI at time of biochemical failure post-EBRT, correlate peak intra-tumoral kPL and kPG with radiotherapy dose distributions from EBRT course. (Part 3)

VIII. For studies incorporating HP 13C-urea, the baseline and the on-treatment changes in urea area under curve (AUC) parameter will be measured and compared to kPL endpoints of the same lesions. (Parts 1-3)

EXPLORATORY OBJECTIVES:

I. To correlate peak intra-tumoral kPL with results of gene expression profiling using Decipher prostate cancer test (DECIPHER) assay.

II. To correlate peak intra-tumoral kPL and kPG with DECIPHER GRID tumor ribonucleic acid (RNA) expression of relevant components of the glycolytic pathway including lactate dehydrogenase (LDH), pyruvate dehydrogenase (PDH), aconitate hydratase (aconitase), MYC, MCT4 (lactate transporter).

III. For patients who undergo optional follow-up HP 13C MRI 6-15 months following baseline scan, determine the mean percent change from baseline in intra-tumoral kPL and kPG and whether the change from baseline is associated change in clinical risk assessment as determined by University of California San Francisco (UCSF) Cancer of the Prostate Risk Assessment (UCSFCAPRA) risk score.

OUTLINE: Patients are assigned to 1 of 4 cohorts.

COHORT 1: Patients receive HP 13C-pyruvate and urea or HP 13C-pyruvate alone intravenously (IV) and undergo standard mpMRI and dynamic HP 13C MRI on day 1. Patients may undergo a second hyperpolarized 13C injection and dynamic HP 13C MRI scan within 15 to 60 minutes following completion of first scan. Patients also undergo blood sample collection during screening.

COHORT 2A: Patients receive HP 13C-pyruvate and urea or HP 13C-pyruvate alone IV and undergo standard mpMRI and dynamic HP 13C MRI on day 1. Patients may optionally receive a follow up mpMRI and HP 13C MRI scan 6-15 months following baseline MRI scans. Patients may optionally undergo transrectal ultrasound (TRUS) or fusion biopsy at week 12. Additionally, patients undergo blood sample collection throughout the study.

COHORT 2B: Patients receive HP 13C-pyruvate and urea or HP 13C-pyruvate alone IV and undergo standard mpMRI and dynamic HP 13C MRI at 0-4 weeks before androgen deprivation therapy (ADT), 4-12 weeks after ADT and prior to the start of radiation therapy, at 3 months post-radiation therapy, and at 1 year post-radiation therapy. Patients also undergo blood sample collection throughout the study.

COHORT3: Patients receive HP 13C-pyruvate and urea or HP 13C-pyruvate alone IV and undergo standard mpMRI and dynamic HP 13C MRI on day 1 and optionally 2-5 years post-radiation therapy in patients with evidence of biochemical failure. Patients may undergo a second hyperpolarized 13C injection and dynamic HP 13C MRI scan within 15 to 60 minutes following completion of first scan. Patients may optionally undergo TRUS or fusion biopsy at week 12. Additionally, patients undergo blood sample collection throughout the study.

Upon completion of study intervention, patients are followed for up to 5 years.